Janine Bestall - Academia.edu (original) (raw)

Papers by Janine Bestall

Fluticasone versus placebo for chronic asthma in adults and children

The Cochrane library, Oct 8, 2008

Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment ... more Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment of asthma. To assess efficacy and safety outcomes in studies that compared FP to placebo for treatment of chronic asthma. We searched the Cochrane Airways Group Specialised Register (January 2008), reference lists of articles, contacted trialists and searched abstracts of major respiratory society meetings (1997-2006). Randomised trials in children and adults comparing FP to placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and risk of bias. Two review authors extracted data. Quantitative analyses were undertaken using Review Manager software. Eighty-six studies met the inclusion criteria, recruiting 16,160 participants. In non-oral steroid treated asthmatics with mild and moderate disease FP resulted in improvements from baseline compared with placebo across all dose ranges (100 to 1000 mcg/d) in FEV1 (between 0.1 to 0.43 litres); morning PEF (between 23 and 46 L/min); symptom scores (based on a standardised scale, between 0.44 and 0.7); reduction in rescue beta-2 agonist use (between 1 and 1.4 puffs/day). High dose FP increased the number of patients who could withdraw from prednisolone: FP 1000-1500 mcg/day Peto Odds Ratio 14.07 (95% CI 7.17 to 27.57). FP at all doses led to a greater likelihood of sore throat, hoarseness and oral Candidiasis. Doses of FP in the range 100-1000 mcg/day are effective. In most patients with mild-moderate asthma improvements with low dose FP are only a little less than those associated with high doses when compared with placebo. High dose FP appears to have worthwhile oral-corticosteroid reducing properties. FP use is accompanied by an increased likelihood of oropharyngeal side effects.

Inhaled fluticasone versus placebo for chronic asthma in adults and children

The Cochrane library, Apr 20, 2005

Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment ... more Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment of asthma. 1. To assess efficacy and safety outcomes in studies that compared FP to placebo for treatment of chronic asthma.2. To explore the presence of a dose-response effect. We searched the Cochrane Airways Group Trial Register (January 2004), reference lists of articles, contacted trialists and searched abstracts of major respiratory society meetings (1997-2004). Randomised trials in children and adults comparing FP to placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality. Two reviewers extracted data. Quantitative analyses where undertaken using RevMan Analyses 4.2.7. Sixty eight studies met the inclusion criteria (11, 104 participants). Methodological quality was high. In non-oral steroid treated asthmatics with mild and moderate disease FP resulted in improvements from baseline compared with placebo across all dose ranges (100 to 1000 mcg/d) in FEV1 (between 0.13 to 0.45 litres); morning PEF (between 27 and 47 L/min); symptom scores (based on a standardised scale, between 0.5 and 0.85); reduction in rescue beta-2 agonist use (between 1.2 and 2.2 puffs/d). High dose FP reduced the number of patients dependent on prednisolone: FP 1000-1500 mcg/d Peto Odds Ratio 0.07 (95% CI 0.05 to 0.10). FP at all doses led to a greater likelihood of sore throat, hoarseness and oral Candidiasis, but 21 patients would need to be treated for one extra to develop Candidiasis (FP 500 mcg/day), whilst only three or four patients need to be treated to avoid one extra patient being withdrawn due to lack of efficacy at all doses of FP. Doses of FP in the range 100-1000 mcg/d are effective. In most patients with mild-moderate asthma improvements with low dose FP are only a little less than those associated with high doses when compared with placebo. High dose FP appears to have worthwhile oral-corticosteroid reducing properties. FP use is accompanied by an increased likelihood of oropharyngeal side effects.

The Cochrane library, Oct 8, 2008

Analysis 1.2. Comparison 1 Parallel group studies, no oral steroids: 50 versus 100 mcg/d (all age... more Analysis 1.2. Comparison 1 Parallel group studies, no oral steroids: 50 versus 100 mcg/d (all ages), Outcome 2 Change in morning

Inhaled fluticasone proprionate for chronic asthma

The Cochrane library, Apr 24, 2000

ABSTRACT Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the t... more ABSTRACT Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment of asthma. 1. To assess efficacy and safety outcomes in studies that compared FP to placebo for treatment of chronic asthma. 2. To explore the presence of a dose-response effect. We searched the Cochrane Airways Group Trial Register (1999), reference lists of articles, contacted trialists and searched abstracts of major respiratory society meetings (1997-1999). Randomised trials in children and adults comparing FP to placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality. One reviewer extracted data. Quantitative analyses where undertaken using Review Manager 4.0.3 with MetaView 3.1. 28 studies were selected for inclusion (5788 subjects). Methodological quality was high. In non-oral steroid treated asthmatics with mild-moderate disease FP produced improvements from baseline compared to placebo: FEV1 Weighted Mean Difference (WMD) 0.31 litres (95% confidence interval (CI) 0.27 to 0.36 litres); morning PEF WMD 29 /min (95% CI 24 to 33 L/min); symptom scores Standardised Mean Difference (SMD) 0.59 (95% CI 0.47 to 0.71); reduction in rescue beta2 agonist use WMD 1.1 puffs/d (95% CI 0.9 to 1.4). Similar effects were seen for all doses up to 1000 mcg/d. A shallow dose response effect was apparent: eg change in morning PEF with FP 1000 mcg/d WMD 49 L/min (95% CI 41 to 58 L/min). High dose FP reduced the number of patients dependent on prednisolone: FP 1000-1500 mcg/d Peto Odds Ratio 0.07 (95% CI 0.05 to 0.10). FP at all doses led to a greater likelihood of sore throat, hoarseness and oral Candidiasis. Doses of FP in the range 100-1000 mcg/d are effective. Although there appears to be a dose-response effect, in most patients with mild-moderate asthma improvements with low dose FP are only a little less than those with high doses. High dose FP appears to have worthwhile oral-corticosteroid reducing properties. FP use is accompanied by an increased likelihood of oropharyngeal side effects and this appears to be dose dependent.

Budesonide at different doses for chronic asthma

The Cochrane library, Apr 24, 2000

Inhaled budesonide (BUD) is available in a range of doses for treating chronic asthma. To quantit... more Inhaled budesonide (BUD) is available in a range of doses for treating chronic asthma. To quantitatively assess the efficacy and safety of budesonide at different doses in order to establish whether a clinically significant dose response profile exists. A search was carried out for Controlled and Randomised Clinical Trials (RCTs) using the Cochrane Airways Group trial register, correspondence with trial authors and the manufacturer. Randomised trials in children and adults comparing one dose of budesonide to a second dose in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality. One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses where undertaken using Review Manager. 24 studies were selected for inclusion in the review (3907 subjects). In non-oral steroid treated, mild to moderately severe asthma no clinically worthwhile differences in FEV1, morning PEFR, symptom scores or rescue beta2 agonist use were apparent across a dose range of 200-1600 mcg/d. However, in moderate to severe asthma there was a significant reduction in the likelihood of trial withdrawal due to asthma exacerbation with BUD 800 mcg/d compared to 200 mcg/d: RR 3.93 (95% CI, 1.4 to 10.9). This result was largely weighted by a single large high quality RCT. In a single study in patients receiving oral corticosteroids, clinically significant improvements favouring high dose BUD (1600 mcg/d) over low dose (200 mcg/d) were apparent for FEV1 and morning PEFR. In two studies there was no dose dependent oral steroid sparing effect for BUD 1600 mcg/d v 800 or 400 mcg/d. Statistically significant, dose dependent suppression of 24 hour urinary free cortisol excretion and serum cortisol post synthetic ACTH infusion over the dose range 800-3200 mcg/d were apparent but the clinical significance of these findings is unclear. Budesonide exhibits a clinically significant dose response effect for improvement in FEV1 in severe asthma and reduction of exacerbations in moderate to severe asthma. No significant dose dependent improvements in FEV1, PEFR or symptoms are evident in non-oral steroid treated asthmatics with mild to moderate disease. Dose dependent alterations in sensitive measures of hypothalamic-pituitary-adrenal function were evident but the clinical significance of these changes is unclear.

Cochrane Database of Systematic Reviews, Apr 20, 2005

Cochrane Database of Systematic Reviews Analysis 2.25. Comparison 2 FP versus BDP or BUD, paralle... more Cochrane Database of Systematic Reviews Analysis 2.25. Comparison 2 FP versus BDP or BUD, parallel studies: dose ratio 1:1, Outcome Withdrawal due to asthma exacerbation

The Cochrane library, Oct 25, 1999

Analysis 2.2. Comparison 2 BDP v BDP: Parallel design, no oral steroids, 400 mcg/d v 800 mcg/d, O... more Analysis 2.2. Comparison 2 BDP v BDP: Parallel design, no oral steroids, 400 mcg/d v 800 mcg/d, Outcome 2 Change in FEV1

Fluticasone versus placebo for chronic asthma in adults and children

Cochrane Database of Systematic Reviews, Oct 19, 2005

Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment ... more Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment of asthma. To assess efficacy and safety outcomes in studies that compared FP to placebo for treatment of chronic asthma. We searched the Cochrane Airways Group Specialised Register (January 2008), reference lists of articles, contacted trialists and searched abstracts of major respiratory society meetings (1997-2006). Randomised trials in children and adults comparing FP to placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and risk of bias. Two review authors extracted data. Quantitative analyses were undertaken using Review Manager software. Eighty-six studies met the inclusion criteria, recruiting 16,160 participants. In non-oral steroid treated asthmatics with mild and moderate disease FP resulted in improvements from baseline compared with placebo across all dose ranges (100 to 1000 mcg/d) in FEV1 (between 0.1 to 0.43 litres); morning PEF (between 23 and 46 L/min); symptom scores (based on a standardised scale, between 0.44 and 0.7); reduction in rescue beta-2 agonist use (between 1 and 1.4 puffs/day). High dose FP increased the number of patients who could withdraw from prednisolone: FP 1000-1500 mcg/day Peto Odds Ratio 14.07 (95% CI 7.17 to 27.57). FP at all doses led to a greater likelihood of sore throat, hoarseness and oral Candidiasis. Doses of FP in the range 100-1000 mcg/day are effective. In most patients with mild-moderate asthma improvements with low dose FP are only a little less than those associated with high doses when compared with placebo. High dose FP appears to have worthwhile oral-corticosteroid reducing properties. FP use is accompanied by an increased likelihood of oropharyngeal side effects.

Cochrane Database of Systematic Reviews, Apr 20, 2005

Background-Chronic heart failure (CHF) is a serious, common condition associated with frequent ho... more Background-Chronic heart failure (CHF) is a serious, common condition associated with frequent hospitalisation. Several different disease management interventions (clinical service organisation interventions) for patients with CHF have been proposed. Objectives-To assess the effectiveness of disease management interventions for patients with CHF.

Inhaled fluticasone versus inhaled beclomethasone or inhaled budesonide for chronic asthma

The Cochrane library, Apr 19, 2004

Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly prescribed inhaled corticoste... more Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly prescribed inhaled corticosteroids for the treatment of asthma, Fluticasone propionate (FP) is newer agent with greater potency in in-vitro assays. To compare the efficacy and safety of Fluticasone to Beclomethasone or Budesonide in the treatment of chronic asthma. We searched the Cochrane Airways Group trial register (January 2003) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997 to 2003). Randomised trials in children and adults comparing Fluticasone to either Beclomethasone or Budesonide in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality. One reviewer extracted data. Quantitative analyses were undertaken using RevMan analyses 1.0.1. 48 studies (11,479 participants) met the inclusion criteria. Methodological quality was variable. When compared at a FP:BUD/BDP dose ratio of 1:2, fluticasone produced a significantly greater FEV1 (Weighted Mean Difference (WMD) 0.11 litres, 95% Confidence Interval (CI) 0.01 to 0.20 litres), morning PEF (WMD 13 L/min, 95%CI 5 to 22 L/min) and evening PEF (WMD 11 L/min, 95%CI 1 to 20 L/min). This applied to all drug doses, age groups, and delivery devices, although subgroup analyses suggested that the relative benefit of FP may be greater in more severe patients treated with higher doses of inhaled corticosteroid. No difference between fluticasone and beclomethasone or budesonide were seen for trial withdrawals (Peto OR 0.76, 95%CI 0.53 to 1.09). Symptoms and rescue medication use were widely reported but few trials provided sufficient data for analysis. A higher likelihood of pharyngitis (Peto Odds Ratio 2.16; 95% CI 1.43 to 3.24) was apparent when patients were treated with fluticasone at twice the dose of BDP/BUD, although there was unexplained heterogeneity in this effect between trials. There was no difference in the likelihood of oral Candidiasis. Plasma cortisol and 24 hour urinary cortisol were measured frequently but data presentation was limited. Fluticasone given at half the daily dose of beclomethasone or budesonide leads to small improvements in measures of airway calibre, but it appears to have a higher risk of causing side-effects when given at the same daily dose.

Journal of Thoracic Oncology, Oct 1, 2018

patients treated with linear accelerator-based SABR between 2009 and 2016 were retrospectively st... more patients treated with linear accelerator-based SABR between 2009 and 2016 were retrospectively studied. Impact of patient, tumor, and treatment parameters on LC, OS and toxicity-free survival (TFS) were evaluated by multivariate analyses. Result: Forty-eight PL and 22 OM lesions were analyzed, including 20 (28%) re-irradiation (Re-RT) cases. Median total, fractionated, and biological equivalent doses in BED10 and BED3 were 55 (30-60), 9.75 (4-18), 110 (41-151), and 228 (90-378) Gy, respectively. Doses given as Re-RT were lower (median Re-RT BED10 dose 94 vs. 110 Gy, P¼0.009). Complete response (CR) was obtained in 43 (61%) lesions. None of the analyzed factors correlated to CR. After a median follow-up of 57 (48-65, 95%CI) months, 10 (14%) lesions had relapsed and 37 (57%) patients had died (2 and 5year LC and OS rates were 84/70% and 52/28%, respectively). In univariate analysis, 2-year LC was lower for lesions with no CR and for colorectal cancer lesions. Only "no CR" was significant (100 vs. 51%; HR¼18.2, CI 2.3-146, P¼0.006) in final multivariate analyses. Median OS was significantly lower in patients with grade 3+ toxicity (5 months after grade 3+ toxicity, vs. 39 months in others [HR 4.7, CI 2-11.2,P<0.0001]). OS was marginally lower in patients with primary lung cancer compared to patients with OM tumors (19 vs. 49 months, HR 2.3, CI 1-5.6, P¼0.06). Among 17 toxicities, 5 reached grade 5. For patients with grade 3+ toxicities, TFS was lower after Re-RT (2-year TFS 63% vs. 96%, HR 5.1, CI 1.3-20.3, P¼0.022) but did not differ significantly for lesions abutting TBT (2-year TFS 69% vs. 93.4%, HR 3.5, CI 0.9-13.9, P¼0.08). Conclusion: SABR is an effective treatment modality in centrally located lung tumors. SABR to re-irradiated lesions and possibly lesions abutting TBT may have the higher risks for serious toxicities. Further studies are indicated.

Implementing the Yorkshire Cancer Research funded Prehabilitation Radiotherapy Exercise smoking Habit cessation And Balanced diet Study (PREHABS): a therapeutic radiographer’s perspective

Lung Cancer, Apr 1, 2023

Implementing the Yorkshire Cancer Research funded Prehabilitation Radiotherapy Exercise smoking Habit cessation And Balanced diet Study (PREHABS): the feasibility of embedding dietetic intervention into the radical lung radiotherapy pathway

Lung Cancer, Apr 1, 2023

The European respiratory journal, Jul 2, 2020

Despite recruiting at a higher rate than previous studies, SABRTooth showed that a large UK RCT w... more Despite recruiting at a higher rate than previous studies, SABRTooth showed that a large UK RCT was not feasible. Patients found it challenging to accept randomisation between surgery and SABR due to their preferences. Alternative study designs are needed. https://bit.ly/2XtlVo6 Cite this article as: Franks KN, McParland L, Webster J, et al. SABRTooth: a randomised controlled feasibility study of stereotactic ablative radiotherapy (SABR) with surgery in patients with peripheral stage I nonsmall cell lung cancer considered to be at higher risk of complications from surgical resection.

Pilot and Feasibility Studies, Feb 1, 2016

Background: Stage I non-small cell lung cancer (NSCLC) is potentially curable, and surgery is con... more Background: Stage I non-small cell lung cancer (NSCLC) is potentially curable, and surgery is considered to be the standard of care for patients with good performance status and minimal co-morbidity. However, a significant proportion of patients with stage I NSCLC have a poorer performance status and significant medical co-morbidity that make them at higher risk of morbidity and mortality from surgery. Stereotactic ablative radiotherapy (SABR), which uses modern radiotherapeutic techniques to deliver large doses of radiation, has shown superiority over conventional radiotherapy in terms of local control and toxicity and is a standard of care for patients with stage I NSCLC who are at too high risk for surgery. However, it is not known whether surgery or SABR is the most effective in patients with stage I NSCLC who are suitable for surgery but are less fit and at higher risk surgical complications. Previous randomised studies have failed to recruit in this setting, and therefore, a feasibility study is required to see whether a full randomised control trial would be possible.

Implementing the Yorkshire Cancer Research funded Prehabilitation Radiotherapy Exercise smoking Habit cessation And Balanced diet Study (PREHABS): the feasibility of embedding dietetic intervention into the radical lung radiotherapy pathway

Lung Cancer

Temporary treatment cessation versus continuation of first-line tyrosine kinase inhibitor in patients with advanced clear cell renal cell carcinoma (STAR): an open-label, non-inferiority, randomised, controlled, phase 2/3 trial

The Lancet Oncology

Pilot and feasibility studies, 2016

After publication of the original article [1], it came to the authors' attention that a source of... more After publication of the original article [1], it came to the authors' attention that a source of funding had been inadvertently omitted from the Acknowledgements section; support from Yorkshire Cancer Research should have mentioned originally.

Holding chambers versus nebulisers for inhaled steroids in chronic asthma

The Cochrane Database of Systematic Reviews, Jan 22, 2001

Inhaled corticosteroids are available in the form of a suspension for nebulisation, although the ... more Inhaled corticosteroids are available in the form of a suspension for nebulisation, although the role of this mode of therapy in the treatment of chronic asthma is still unclear. To assess the efficacy and safety of inhaled corticosteroids delivered via nebuliser versus holding chamber for the treatment of chronic asthma. We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted the authors of studies and pharmaceutical companies for additional studies and hand-searched the British Journal of Clinical Research, European Journal of Clinical Research and major respiratory society meeting abstracts (1997-1999). Randomised controlled trials comparing nebuliser to holding chamber in the delivery of inhaled corticosteroids for the treatment of chronic asthma. All age groups of patients were considered. Two reviewers assessed articles for inclusion; two reviewers independently assessed included studies for methodological quality. One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses were undertaken using Review Manager 4.1 with MetaView 3.1. Two studies were selected for inclusion (63 subjects), both concerned adults. Methodological quality was variable. Due to design differences it was not appropriate to pool the studies. The single high quality study compared budesonide 2000-8000 mcg delivered via Pari Inhalier Boy jet nebuliser with inspiration-only inhalation to budesonide 1600 mcg via large volume spacer. The nebuliser delivery led to higher morning peak expiratory flow values (25 L/min p&lt;0.01), higher evening values (30L/min, p&lt;0.01), lower rescue beta2 agonist use and symptom scores compared to the holding chamber delivery. Budesonide in high dose delivered by the particular nebuliser used in the only double-blinded study that could be included in this review was more effective than budesonide 1600 mcg via a large volume spacer. However, it is not clear whether this was an effect of nominal dose delivered or delivery system. Cost, compliance and patient preference are important determinants of clinical effectiveness that have not been assessed. Future studies are needed to evaluate the relative effectiveness of inhaled corticosteroids delivered by different combinations of nebuliser/compressor compared to holding chamber. Moreover, further studies assessing these delivery methods are needed in infants and pre-school children, as these are groups that are likely to be considered for treatment with nebulised corticosteroids.

A randomised phase III multicentre trial to evaluate the duration of anti-PD1 monoclonal antibody monotherapy in patients with metastatic melanoma (DANTE) - Stage 1 Results

Fluticasone versus placebo for chronic asthma in adults and children

The Cochrane library, Oct 8, 2008

Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment ... more Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment of asthma. To assess efficacy and safety outcomes in studies that compared FP to placebo for treatment of chronic asthma. We searched the Cochrane Airways Group Specialised Register (January 2008), reference lists of articles, contacted trialists and searched abstracts of major respiratory society meetings (1997-2006). Randomised trials in children and adults comparing FP to placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and risk of bias. Two review authors extracted data. Quantitative analyses were undertaken using Review Manager software. Eighty-six studies met the inclusion criteria, recruiting 16,160 participants. In non-oral steroid treated asthmatics with mild and moderate disease FP resulted in improvements from baseline compared with placebo across all dose ranges (100 to 1000 mcg/d) in FEV1 (between 0.1 to 0.43 litres); morning PEF (between 23 and 46 L/min); symptom scores (based on a standardised scale, between 0.44 and 0.7); reduction in rescue beta-2 agonist use (between 1 and 1.4 puffs/day). High dose FP increased the number of patients who could withdraw from prednisolone: FP 1000-1500 mcg/day Peto Odds Ratio 14.07 (95% CI 7.17 to 27.57). FP at all doses led to a greater likelihood of sore throat, hoarseness and oral Candidiasis. Doses of FP in the range 100-1000 mcg/day are effective. In most patients with mild-moderate asthma improvements with low dose FP are only a little less than those associated with high doses when compared with placebo. High dose FP appears to have worthwhile oral-corticosteroid reducing properties. FP use is accompanied by an increased likelihood of oropharyngeal side effects.

Inhaled fluticasone versus placebo for chronic asthma in adults and children

The Cochrane library, Apr 20, 2005

Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment ... more Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment of asthma. 1. To assess efficacy and safety outcomes in studies that compared FP to placebo for treatment of chronic asthma.2. To explore the presence of a dose-response effect. We searched the Cochrane Airways Group Trial Register (January 2004), reference lists of articles, contacted trialists and searched abstracts of major respiratory society meetings (1997-2004). Randomised trials in children and adults comparing FP to placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality. Two reviewers extracted data. Quantitative analyses where undertaken using RevMan Analyses 4.2.7. Sixty eight studies met the inclusion criteria (11, 104 participants). Methodological quality was high. In non-oral steroid treated asthmatics with mild and moderate disease FP resulted in improvements from baseline compared with placebo across all dose ranges (100 to 1000 mcg/d) in FEV1 (between 0.13 to 0.45 litres); morning PEF (between 27 and 47 L/min); symptom scores (based on a standardised scale, between 0.5 and 0.85); reduction in rescue beta-2 agonist use (between 1.2 and 2.2 puffs/d). High dose FP reduced the number of patients dependent on prednisolone: FP 1000-1500 mcg/d Peto Odds Ratio 0.07 (95% CI 0.05 to 0.10). FP at all doses led to a greater likelihood of sore throat, hoarseness and oral Candidiasis, but 21 patients would need to be treated for one extra to develop Candidiasis (FP 500 mcg/day), whilst only three or four patients need to be treated to avoid one extra patient being withdrawn due to lack of efficacy at all doses of FP. Doses of FP in the range 100-1000 mcg/d are effective. In most patients with mild-moderate asthma improvements with low dose FP are only a little less than those associated with high doses when compared with placebo. High dose FP appears to have worthwhile oral-corticosteroid reducing properties. FP use is accompanied by an increased likelihood of oropharyngeal side effects.

The Cochrane library, Oct 8, 2008

Analysis 1.2. Comparison 1 Parallel group studies, no oral steroids: 50 versus 100 mcg/d (all age... more Analysis 1.2. Comparison 1 Parallel group studies, no oral steroids: 50 versus 100 mcg/d (all ages), Outcome 2 Change in morning

Inhaled fluticasone proprionate for chronic asthma

The Cochrane library, Apr 24, 2000

ABSTRACT Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the t... more ABSTRACT Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment of asthma. 1. To assess efficacy and safety outcomes in studies that compared FP to placebo for treatment of chronic asthma. 2. To explore the presence of a dose-response effect. We searched the Cochrane Airways Group Trial Register (1999), reference lists of articles, contacted trialists and searched abstracts of major respiratory society meetings (1997-1999). Randomised trials in children and adults comparing FP to placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality. One reviewer extracted data. Quantitative analyses where undertaken using Review Manager 4.0.3 with MetaView 3.1. 28 studies were selected for inclusion (5788 subjects). Methodological quality was high. In non-oral steroid treated asthmatics with mild-moderate disease FP produced improvements from baseline compared to placebo: FEV1 Weighted Mean Difference (WMD) 0.31 litres (95% confidence interval (CI) 0.27 to 0.36 litres); morning PEF WMD 29 /min (95% CI 24 to 33 L/min); symptom scores Standardised Mean Difference (SMD) 0.59 (95% CI 0.47 to 0.71); reduction in rescue beta2 agonist use WMD 1.1 puffs/d (95% CI 0.9 to 1.4). Similar effects were seen for all doses up to 1000 mcg/d. A shallow dose response effect was apparent: eg change in morning PEF with FP 1000 mcg/d WMD 49 L/min (95% CI 41 to 58 L/min). High dose FP reduced the number of patients dependent on prednisolone: FP 1000-1500 mcg/d Peto Odds Ratio 0.07 (95% CI 0.05 to 0.10). FP at all doses led to a greater likelihood of sore throat, hoarseness and oral Candidiasis. Doses of FP in the range 100-1000 mcg/d are effective. Although there appears to be a dose-response effect, in most patients with mild-moderate asthma improvements with low dose FP are only a little less than those with high doses. High dose FP appears to have worthwhile oral-corticosteroid reducing properties. FP use is accompanied by an increased likelihood of oropharyngeal side effects and this appears to be dose dependent.

Budesonide at different doses for chronic asthma

The Cochrane library, Apr 24, 2000

Inhaled budesonide (BUD) is available in a range of doses for treating chronic asthma. To quantit... more Inhaled budesonide (BUD) is available in a range of doses for treating chronic asthma. To quantitatively assess the efficacy and safety of budesonide at different doses in order to establish whether a clinically significant dose response profile exists. A search was carried out for Controlled and Randomised Clinical Trials (RCTs) using the Cochrane Airways Group trial register, correspondence with trial authors and the manufacturer. Randomised trials in children and adults comparing one dose of budesonide to a second dose in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality. One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses where undertaken using Review Manager. 24 studies were selected for inclusion in the review (3907 subjects). In non-oral steroid treated, mild to moderately severe asthma no clinically worthwhile differences in FEV1, morning PEFR, symptom scores or rescue beta2 agonist use were apparent across a dose range of 200-1600 mcg/d. However, in moderate to severe asthma there was a significant reduction in the likelihood of trial withdrawal due to asthma exacerbation with BUD 800 mcg/d compared to 200 mcg/d: RR 3.93 (95% CI, 1.4 to 10.9). This result was largely weighted by a single large high quality RCT. In a single study in patients receiving oral corticosteroids, clinically significant improvements favouring high dose BUD (1600 mcg/d) over low dose (200 mcg/d) were apparent for FEV1 and morning PEFR. In two studies there was no dose dependent oral steroid sparing effect for BUD 1600 mcg/d v 800 or 400 mcg/d. Statistically significant, dose dependent suppression of 24 hour urinary free cortisol excretion and serum cortisol post synthetic ACTH infusion over the dose range 800-3200 mcg/d were apparent but the clinical significance of these findings is unclear. Budesonide exhibits a clinically significant dose response effect for improvement in FEV1 in severe asthma and reduction of exacerbations in moderate to severe asthma. No significant dose dependent improvements in FEV1, PEFR or symptoms are evident in non-oral steroid treated asthmatics with mild to moderate disease. Dose dependent alterations in sensitive measures of hypothalamic-pituitary-adrenal function were evident but the clinical significance of these changes is unclear.

Cochrane Database of Systematic Reviews, Apr 20, 2005

Cochrane Database of Systematic Reviews Analysis 2.25. Comparison 2 FP versus BDP or BUD, paralle... more Cochrane Database of Systematic Reviews Analysis 2.25. Comparison 2 FP versus BDP or BUD, parallel studies: dose ratio 1:1, Outcome Withdrawal due to asthma exacerbation

The Cochrane library, Oct 25, 1999

Analysis 2.2. Comparison 2 BDP v BDP: Parallel design, no oral steroids, 400 mcg/d v 800 mcg/d, O... more Analysis 2.2. Comparison 2 BDP v BDP: Parallel design, no oral steroids, 400 mcg/d v 800 mcg/d, Outcome 2 Change in FEV1

Fluticasone versus placebo for chronic asthma in adults and children

Cochrane Database of Systematic Reviews, Oct 19, 2005

Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment ... more Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment of asthma. To assess efficacy and safety outcomes in studies that compared FP to placebo for treatment of chronic asthma. We searched the Cochrane Airways Group Specialised Register (January 2008), reference lists of articles, contacted trialists and searched abstracts of major respiratory society meetings (1997-2006). Randomised trials in children and adults comparing FP to placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and risk of bias. Two review authors extracted data. Quantitative analyses were undertaken using Review Manager software. Eighty-six studies met the inclusion criteria, recruiting 16,160 participants. In non-oral steroid treated asthmatics with mild and moderate disease FP resulted in improvements from baseline compared with placebo across all dose ranges (100 to 1000 mcg/d) in FEV1 (between 0.1 to 0.43 litres); morning PEF (between 23 and 46 L/min); symptom scores (based on a standardised scale, between 0.44 and 0.7); reduction in rescue beta-2 agonist use (between 1 and 1.4 puffs/day). High dose FP increased the number of patients who could withdraw from prednisolone: FP 1000-1500 mcg/day Peto Odds Ratio 14.07 (95% CI 7.17 to 27.57). FP at all doses led to a greater likelihood of sore throat, hoarseness and oral Candidiasis. Doses of FP in the range 100-1000 mcg/day are effective. In most patients with mild-moderate asthma improvements with low dose FP are only a little less than those associated with high doses when compared with placebo. High dose FP appears to have worthwhile oral-corticosteroid reducing properties. FP use is accompanied by an increased likelihood of oropharyngeal side effects.

Cochrane Database of Systematic Reviews, Apr 20, 2005

Background-Chronic heart failure (CHF) is a serious, common condition associated with frequent ho... more Background-Chronic heart failure (CHF) is a serious, common condition associated with frequent hospitalisation. Several different disease management interventions (clinical service organisation interventions) for patients with CHF have been proposed. Objectives-To assess the effectiveness of disease management interventions for patients with CHF.

Inhaled fluticasone versus inhaled beclomethasone or inhaled budesonide for chronic asthma

The Cochrane library, Apr 19, 2004

Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly prescribed inhaled corticoste... more Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly prescribed inhaled corticosteroids for the treatment of asthma, Fluticasone propionate (FP) is newer agent with greater potency in in-vitro assays. To compare the efficacy and safety of Fluticasone to Beclomethasone or Budesonide in the treatment of chronic asthma. We searched the Cochrane Airways Group trial register (January 2003) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997 to 2003). Randomised trials in children and adults comparing Fluticasone to either Beclomethasone or Budesonide in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality. One reviewer extracted data. Quantitative analyses were undertaken using RevMan analyses 1.0.1. 48 studies (11,479 participants) met the inclusion criteria. Methodological quality was variable. When compared at a FP:BUD/BDP dose ratio of 1:2, fluticasone produced a significantly greater FEV1 (Weighted Mean Difference (WMD) 0.11 litres, 95% Confidence Interval (CI) 0.01 to 0.20 litres), morning PEF (WMD 13 L/min, 95%CI 5 to 22 L/min) and evening PEF (WMD 11 L/min, 95%CI 1 to 20 L/min). This applied to all drug doses, age groups, and delivery devices, although subgroup analyses suggested that the relative benefit of FP may be greater in more severe patients treated with higher doses of inhaled corticosteroid. No difference between fluticasone and beclomethasone or budesonide were seen for trial withdrawals (Peto OR 0.76, 95%CI 0.53 to 1.09). Symptoms and rescue medication use were widely reported but few trials provided sufficient data for analysis. A higher likelihood of pharyngitis (Peto Odds Ratio 2.16; 95% CI 1.43 to 3.24) was apparent when patients were treated with fluticasone at twice the dose of BDP/BUD, although there was unexplained heterogeneity in this effect between trials. There was no difference in the likelihood of oral Candidiasis. Plasma cortisol and 24 hour urinary cortisol were measured frequently but data presentation was limited. Fluticasone given at half the daily dose of beclomethasone or budesonide leads to small improvements in measures of airway calibre, but it appears to have a higher risk of causing side-effects when given at the same daily dose.

Journal of Thoracic Oncology, Oct 1, 2018

patients treated with linear accelerator-based SABR between 2009 and 2016 were retrospectively st... more patients treated with linear accelerator-based SABR between 2009 and 2016 were retrospectively studied. Impact of patient, tumor, and treatment parameters on LC, OS and toxicity-free survival (TFS) were evaluated by multivariate analyses. Result: Forty-eight PL and 22 OM lesions were analyzed, including 20 (28%) re-irradiation (Re-RT) cases. Median total, fractionated, and biological equivalent doses in BED10 and BED3 were 55 (30-60), 9.75 (4-18), 110 (41-151), and 228 (90-378) Gy, respectively. Doses given as Re-RT were lower (median Re-RT BED10 dose 94 vs. 110 Gy, P¼0.009). Complete response (CR) was obtained in 43 (61%) lesions. None of the analyzed factors correlated to CR. After a median follow-up of 57 (48-65, 95%CI) months, 10 (14%) lesions had relapsed and 37 (57%) patients had died (2 and 5year LC and OS rates were 84/70% and 52/28%, respectively). In univariate analysis, 2-year LC was lower for lesions with no CR and for colorectal cancer lesions. Only "no CR" was significant (100 vs. 51%; HR¼18.2, CI 2.3-146, P¼0.006) in final multivariate analyses. Median OS was significantly lower in patients with grade 3+ toxicity (5 months after grade 3+ toxicity, vs. 39 months in others [HR 4.7, CI 2-11.2,P<0.0001]). OS was marginally lower in patients with primary lung cancer compared to patients with OM tumors (19 vs. 49 months, HR 2.3, CI 1-5.6, P¼0.06). Among 17 toxicities, 5 reached grade 5. For patients with grade 3+ toxicities, TFS was lower after Re-RT (2-year TFS 63% vs. 96%, HR 5.1, CI 1.3-20.3, P¼0.022) but did not differ significantly for lesions abutting TBT (2-year TFS 69% vs. 93.4%, HR 3.5, CI 0.9-13.9, P¼0.08). Conclusion: SABR is an effective treatment modality in centrally located lung tumors. SABR to re-irradiated lesions and possibly lesions abutting TBT may have the higher risks for serious toxicities. Further studies are indicated.

Implementing the Yorkshire Cancer Research funded Prehabilitation Radiotherapy Exercise smoking Habit cessation And Balanced diet Study (PREHABS): a therapeutic radiographer’s perspective

Lung Cancer, Apr 1, 2023

Implementing the Yorkshire Cancer Research funded Prehabilitation Radiotherapy Exercise smoking Habit cessation And Balanced diet Study (PREHABS): the feasibility of embedding dietetic intervention into the radical lung radiotherapy pathway

Lung Cancer, Apr 1, 2023

The European respiratory journal, Jul 2, 2020

Despite recruiting at a higher rate than previous studies, SABRTooth showed that a large UK RCT w... more Despite recruiting at a higher rate than previous studies, SABRTooth showed that a large UK RCT was not feasible. Patients found it challenging to accept randomisation between surgery and SABR due to their preferences. Alternative study designs are needed. https://bit.ly/2XtlVo6 Cite this article as: Franks KN, McParland L, Webster J, et al. SABRTooth: a randomised controlled feasibility study of stereotactic ablative radiotherapy (SABR) with surgery in patients with peripheral stage I nonsmall cell lung cancer considered to be at higher risk of complications from surgical resection.

Pilot and Feasibility Studies, Feb 1, 2016

Background: Stage I non-small cell lung cancer (NSCLC) is potentially curable, and surgery is con... more Background: Stage I non-small cell lung cancer (NSCLC) is potentially curable, and surgery is considered to be the standard of care for patients with good performance status and minimal co-morbidity. However, a significant proportion of patients with stage I NSCLC have a poorer performance status and significant medical co-morbidity that make them at higher risk of morbidity and mortality from surgery. Stereotactic ablative radiotherapy (SABR), which uses modern radiotherapeutic techniques to deliver large doses of radiation, has shown superiority over conventional radiotherapy in terms of local control and toxicity and is a standard of care for patients with stage I NSCLC who are at too high risk for surgery. However, it is not known whether surgery or SABR is the most effective in patients with stage I NSCLC who are suitable for surgery but are less fit and at higher risk surgical complications. Previous randomised studies have failed to recruit in this setting, and therefore, a feasibility study is required to see whether a full randomised control trial would be possible.

Implementing the Yorkshire Cancer Research funded Prehabilitation Radiotherapy Exercise smoking Habit cessation And Balanced diet Study (PREHABS): the feasibility of embedding dietetic intervention into the radical lung radiotherapy pathway

Lung Cancer

Temporary treatment cessation versus continuation of first-line tyrosine kinase inhibitor in patients with advanced clear cell renal cell carcinoma (STAR): an open-label, non-inferiority, randomised, controlled, phase 2/3 trial

The Lancet Oncology

Pilot and feasibility studies, 2016

After publication of the original article [1], it came to the authors' attention that a source of... more After publication of the original article [1], it came to the authors' attention that a source of funding had been inadvertently omitted from the Acknowledgements section; support from Yorkshire Cancer Research should have mentioned originally.

Holding chambers versus nebulisers for inhaled steroids in chronic asthma

The Cochrane Database of Systematic Reviews, Jan 22, 2001

Inhaled corticosteroids are available in the form of a suspension for nebulisation, although the ... more Inhaled corticosteroids are available in the form of a suspension for nebulisation, although the role of this mode of therapy in the treatment of chronic asthma is still unclear. To assess the efficacy and safety of inhaled corticosteroids delivered via nebuliser versus holding chamber for the treatment of chronic asthma. We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted the authors of studies and pharmaceutical companies for additional studies and hand-searched the British Journal of Clinical Research, European Journal of Clinical Research and major respiratory society meeting abstracts (1997-1999). Randomised controlled trials comparing nebuliser to holding chamber in the delivery of inhaled corticosteroids for the treatment of chronic asthma. All age groups of patients were considered. Two reviewers assessed articles for inclusion; two reviewers independently assessed included studies for methodological quality. One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses were undertaken using Review Manager 4.1 with MetaView 3.1. Two studies were selected for inclusion (63 subjects), both concerned adults. Methodological quality was variable. Due to design differences it was not appropriate to pool the studies. The single high quality study compared budesonide 2000-8000 mcg delivered via Pari Inhalier Boy jet nebuliser with inspiration-only inhalation to budesonide 1600 mcg via large volume spacer. The nebuliser delivery led to higher morning peak expiratory flow values (25 L/min p&lt;0.01), higher evening values (30L/min, p&lt;0.01), lower rescue beta2 agonist use and symptom scores compared to the holding chamber delivery. Budesonide in high dose delivered by the particular nebuliser used in the only double-blinded study that could be included in this review was more effective than budesonide 1600 mcg via a large volume spacer. However, it is not clear whether this was an effect of nominal dose delivered or delivery system. Cost, compliance and patient preference are important determinants of clinical effectiveness that have not been assessed. Future studies are needed to evaluate the relative effectiveness of inhaled corticosteroids delivered by different combinations of nebuliser/compressor compared to holding chamber. Moreover, further studies assessing these delivery methods are needed in infants and pre-school children, as these are groups that are likely to be considered for treatment with nebulised corticosteroids.

A randomised phase III multicentre trial to evaluate the duration of anti-PD1 monoclonal antibody monotherapy in patients with metastatic melanoma (DANTE) - Stage 1 Results